Biokinetic models evaluation

An integrated testing strategy is any approach to the evaluation of toxicity which serves to reduce, refine or replace an existing animal procedure, and which is based on the use of two or more of the following physicochemical, in vitro, human (e.g., epidemiological, clinical case reports), and animal data (where unavoidable), and computational methods, such as (quantitative) structure-activity relationships ([Q]SAR) and biokinetic models. 

International Commission on Radiological Protection (1987a) Technetium-DTPA. In Annals of the ICRP, radiation dose to patients from radiopharmaceuticals, biokinetic models and data. ICRP publication 53, vol 18, no 1-4. Pergamon, Oxford, pp 187-190 International Commission on Radiological Protection (1987b) Technetium-labelled aerosols. In Annals of the ICRP, radiation dose to patients from radiopharmaceuticals, biokinetic models and data. ICRP publication 53, vol 18, no 1-4. Pergamon, Oxford, pp 217-219 Kadir S, Strauss WH (1979) Evaluation of inflammatory bowel disease with Tc-99m-DTPA. Radiology 130 443-446... 

The bioassays developed for assessment of the internal uranium contamination (body burden) are capable of regularly determining the uranium content in urine, feces, hair, nails, bones, and teeth samples. Biokinetic models use the results of these measurements to evaluate the body burden, but it should be kept in mind that these general models may not apply exactly to each individual, so there is quite a large uncertainty that is built-in to the assessment of internal exposure. We have preseuted the analytical methods and procedures used for the measurements and have tried to demonstrate the variability and complexity of the methods. 

Application of biokinetic models to actual exposure populations first requires steps to determine the relative reliability of the particular model. Two critical steps are sensitivity analysis and model evaluation. The first judges the assumptions within the model and magnitude of the predicted response. The latter assesses the degree of concordance between simulation and observation. 

A critical component of evaluating risk groups exposures to Pb is the sampling of case-specific environmental media known to provide pathways from Pb source to human receptor(s). Using environmental data with measured PbB values provides for regression analysis modehng. Use of environmental data is also desirable and often necessary in order to use biokinetic models, such as the lEUBK model. 

The lEUBK predictive model was used extensively in these non-Box Basin studies. As for the Box evaluations, the biokinetic modeling was necessary for evaluating responses of PbB simulations to environmentally variable media Pb inputs and calibrations for intake—uptake parameters and for determining risk levels linked to various Pb input scenarios. Table 23.9 indicates the concordance between measured and predicted PbB levels for the non-Box subjects and environmental data sets using either default or indicated bioavailability and dust/soil ratios. The site-specific partitioning values... 

Analysis of the particle size and solubility of samples of airborne radioactive material can assist in the development of biokinetic models for dose assessment (Section 6). Direct comparison of air samples with values of derived air concentrations (Section 2) can be used as an input to the evaluation of workplace conditions and to the estimation of doses. 

The biokinetic models developed by the ICRP are intended for use in normal situations for example for the evaluation of doses fiom measurements performed aeeording to routine monitoring programmes. The evaluation of doses in accident situations needs more specific information about the time and pattern of intake, about the physicochemieal form of the radionuctides and about the eharacteristics of the individual (e.g. body mass). Individual spedfie data on the biokinetics of radio-nuclide(s) may be obtained through speeial monitoring, i.e. by repeated direct measurements of the whole body or speeifie sites and measurements of excretion. 

Figure 2.17. Flowchart of adaptive modeling in the integrating strategy, applying deductive research methodology in which mathematical models (for physical transports Wj, biokinetics and stoichiometry on the macroscopic level Y j or the microscopic level Vjij) serve as working hypotheses to be compared consequently with carefully designed and evaluated experiments. Special attention concerns the interactions between j, Tj, and as indicated. (From Moser, 1981).

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